Sunday, June 28, 2009

I have often seen milk thistle (silymarin) touted as a shining star among natural remedies for hepatoprotective benefits. And although still controversial, it is intriguing to learn of its antiperoxidative effects in achieving small increases in glutathione levels (1).

No doubt that a 2008 meta-analysis from Switzerland on silymarin will pique your interest further. After reviewing the only 19 available "double-blind" and "single-blind" studies, no evidence was found to help with viral hepatitis, but in liver cirrhosis sylimarin was able to reduce aspartate aminotransferase, although not alkaline phosphatase (2)--this means it may help protect hepatocytes (liver cells).

The meta-analysis concluded that not enough clinical evidence existed for proper recommendation (2). But risk/benefit analysis would suggest it's reasonable to use sylimarin as a therapy for poisoning and may have minor benefit in liver cirrhosis (2).

Troponin is a three-subunit protein complex that regulates striated (skeletal and cardiac) muscle contraction (1-3). Similar to caldesmon in smooth muscle, troponin affects release from actin (3). The process of muscle contraction is best represented by the sliding filament model (3). The model illustrates heavy dependence on calcium regulation for velocity involving “loose coupling” of calcium binding to troponin to determine the rate of “cycling cross-bridges” (4-6).

Cross-bridge cycling is a two-feedback mechanism—positive and negative—depending on its activation and regulation (6). Troponin subunit Tn-T is attached to tropomyocin is attached to actin (3). When a signal transmitted to the sarcoplasmic reticulum induces release of Ca(2+) into the sarcomere, then the Ca(2+) binds to subunit Tn-C, which changes orientation of subunit Tn-I (3). The Tn-I change causes a rotation in which the structure of tropomyosin rotates actin and exposes it to myosin binding sites creating contractibility (3). This action is critical in the heart (1). It’s worth noting that any mutations of cardiac troponin would affect this process, which develops cardiomyopathies (1;7). Contraction is stopped by ATPase pumping Ca(2+) out of the sarcomere furiously (3). Once in the sarcoplastmic reticulum, the Ca(2+) is taken away by calsequestrin (3).

As a diagnostic tool for myocardial infarction, troponins are highly valued because they can detect the smallest of infarctions in comparison to other cardiac markers such as electrocardiogram, creatine kinase (CK) and CK-MB (2). Tn-T can be expressed from skeletal muscle, but Tn-I is specific to myocardium (1). Any elevation of cardiac troponins are serious markers that largely indicate a poor prognosis with unstable angina (2).

Forty-two hours after ingesting an unknown mushroom, a 56-year-old man was admitted to a Turkish emergency department (1). Cardiac markers troponin I, creatine kinase (CK), CK-MB isoenzyme, and myoglobin were all elevated (1). The testing detected nothing less than myocardial infarction (2). This diagnosis, however, was not correct.

The clinicians noted in their report that despite the potentially confusing cardiac markers, the patient was diagnosed with hepatic and renal falure (1). This is because in cases of mushroom poisoning, “amatoxins” bind with “actin filaments within myocardiocytes or renal cells and/or its effects as circulating antitropin antibodies” causing the cardiac markers to become elevated (1).

The patient was treated with fluids, activated charcoal, antibiotics and silibinin (an active constituent of milk thistle) and improvement followed (1).

Saturday, June 27, 2009

Omega-3 fatty acids from fish have largely stolen the spotlight for anti-depression, but recent evidence finds that oleic acid from olive oil may also be useful in women.

Last May a 10-year national cohort followed 1,947 men and 2,909 women (African-American and Caucasian) (1). They were separated according to “lowest, middle and highest” for oleic fatty acid intake as well as linoleic (omega-6) fatty acid intake (1). Estimates adjusted for fish consumption and diseases (1).

The researchers found linoleic acid was associated with increased risk of severe depression in men and that oleic acid (omega-9) was associated with a reduced risk of severe depression in women (1).

Popeye take note.

Depression, Gone Fishing

Stroll along the bank of river peacefully, bait your hook, cast, enjoy a beer. The fish themselves may not think so, but going fishing is a relaxing pastime. But don’t catch and release because eating those fish may even more of a mood booster. Well, that may be a stretch.

Truth is that a dietary deficiency of omega-3 fatty acids—found in amounts highest in fatty fish—may be related to great risk of depression, particularly among pregnant or menopausal women, according to recent studies (2-6).

Scientists have known for a while that an association between omega-3 fatty acids and depression exists, but it is still unclear why and its use as a single therapy has not been found to be effective; still researchers hope omega-3 oils can be used as complementary nutritional therapy to other treatments (2;7-10).

In fact, omega-3 was reconfirmed earlier this month by the Emory University School of Medicine to have a place as in researching emerging targets for antidepressant therapies (11;12). This is in light of frustration of failure of current treatments of depression drugs such as monoamine reuptake inhibitors and nutritional interventions to provide results (7;12).

The plethora of scientific studies on lipids and nutrition would have nutritionists thinking within reason that omega-3s are the chosen fatty acid to deliver humankind from sickness. But despite the seemingly omnipotent oil’s overabundance of qualities, not nearly enough is known about how much to consume in relation to other fatty acids such as omega-6.

In June 2008, top cardiologists convened to examine all clinical evidence and discuss optimal omega-3 dosages (1). The conclusions were summarized with a recommendation of at least 250 mg of DHA and EPA fatty acids for the “primary prevention of cardiovascular disease” (1). No ratio recommendation was given, which was purposeful.

In fact, the focus on omega-3 to omega-6 ratios had been heavily criticized earlier. A report in 2007 by the UK Food Standards Agency said that “ratio is not a useful concept and it distracts attention away from absolute intakes” (2). And a year earlier, top American omega-3 fatty acid researcher William S. Harris, Ph.D., of University of South Dakota’s Nutrition and Metabolic Diseases Research Institute wrote that “although initially appealing” for making nutritional recommendations, ratio is “of little value” (3). Lacking clinical data, the UK Food Standards Agency, Dr Harris and others may be correct in calling for concentration solely on omega-3 for established treatment(4;5).

Many clinicians and researchers, however, continue to advise and perform studies from the theoretical viewpoint of a ratio. A microscopic view reveals answers to why. The function of omega-3 and omega-6 in the cell or an organ such as the liver or brain highlights key differences. Dr Harris does concede these facts: that the two fatty acids compete for enzymes and have opposite effects (3). In addition to omega-3’s anti-inflammatory and omega-6’s inflammatory uniqueness (6), the biochemistry also presents information on how each influences metabolism, genetic expression (6-10), cell membrane function and neurotransmission (6;11). While insightful, however, the information does stop short of any clinical parameters.

As a base for perspective, nutritionists find it useful to turn to dietary origins. Nutritional anthropology and epidemiological studies suggest a ratio of 1-2:1 omega-6 to omega-3, which is in large contrast to the typical Western diet of 15-16:1 (6;12-15). And many ratios resembling the ideal hunter-gatherer 1:1 do propose significant reduction of risk of chronic disease, mainly coronary artery disease and arthritis (6;15). These research approaches come with caution as they are not enough for science in absolute, nor do they offer indication of any exact amounts for best efficacy.

Truer data must come from well-designed randomized, double-blind controlled trials. To reflect proper indications, these studies should take into account ratio, amounts or both. An example of a trial was conducted in 2003 when two parallel groups of 15 patients who each had major elective abdominal surgery were given omega-6 to omega-3 ratio of 3:1, which confirmed a significant anti-inflammatory effect (16). More trials such as this one could illuminate further.

Sunday, June 21, 2009

Acute tubular necrosis (ATN) is a condition resulting from tubular cell apoptosis contributing to renal failure (1-3). It can result due to insult from extensive injury such as acute blood loss or septic shock, a specific renal disease such as glomerulonephritis, nephrotoxic drugs or bacterial products, or hypoxia (1-3).

ATN is identified via a rising serum urea creatinine and can be classified as pre-renal, renal or post-renal (1). If identified early, corrective action can stop damage and possible hyperkalemia (1).

Glomerulonephritis is an inflammation of the glomeruli, which causes progressive renal damage that can lead to ATN and renal failure (4-6). The disease is mainly caused by infection such as streptococcal infection (7;8). In post-streptococcal glomerulonephritis, symptoms can include sudden hypertension, proteinuria, edema and hematuria (9). The inflammatory response causing the damage to the kidneys is thought to be related to hypersensitive immune response (9). Maintenance generally can include treatment of underlying disease, balancing electrolytes and fluids, and possible peritoneal dialysis (10).

What effects do you think alcohol consumption could have on renal function tests?

You’ve heard before that alcohol in moderation (in moderation!) may be good for your heart, but what can it do to your kidneys? Acute and chronic alcohol consumption does alter renal function and other physiological processes such as blood flow and fluid and electrolyte balances, which can directly affect results of renal function tests (1;2). Effects include higher level of creatine clearance and glomerular filtration rate (3). The alterations are especially noticeable in cases of liver disease (1;2).

Heavy drinking—which would be four or more alcoholic drinks a day—has a strong correlation with chronic kidney disease, especially in patients who smoke, have diabetes or hypertension or who are obese (4). When under condition of liver cirrhosis, chronic alcohol intake has been shown in rats and humans to possibly play a role in causing kidney enlargement and alterations in tubules (1). This all suggests renal detriment from consumption of alcohol.

However, prospective cohorts on moderate consumption in men and women tell a different story. A 2005 study on 11,023 healthy men over 14 years found that while there was association between alcohol consumption and glomerular filtration rates, moderate alcohol consumption actually caused a lower risk of renal dysfunction over time (5). A 2005 study on 1,658 female nurses for 11 years showed similar data in that while glomerular filtration rate was affected, moederate alcohol consumption had no adverse effect on renal dysfunction over time (2).

Why isn’t a total urine volume taken over 24 hours enough to assess renal function?

A total 24-hour urine volume can be useful for identifying reduced or increased urine volume, but it is unreliable (not to mention inconvenient) and still not enough to identify renal dysfunction or failure (it can simply indicate dehydration, high fluid intake or use of diuretics) (1-3).

The measurement of urinary excretion of creatinine of the 24-hour urine volume, called creatinine clearance, reveals more because it can better indicate glomerular filtration rate (GFR) (1;2). However, creatine clearance is still limited in its precision due to possible confounding variables (1).

An approach to support proper investigation into renal function should include other measures inclindin estimated GFR (considering age, sex, ethinicity and weight) as well as tests for other markers of clearance such as cystatin C (a protein almost unaffected by meat intake), inulin (most accurate estimate of GFR) and albumin (indicator of proteinuria) (1).

Apart from GFR, in cases of possible renal tubular dysfunction measurement of tubular reabsorption is necessary because it may contribute to acute renal failure (1). Usually tubular damage occurs due to other conditions (1). Examination may include osmolality measurements of plasma and urine, water deprivation tests, urine pH and acid load tests, specific proteinuria, aminoaciduria or glycosuria tests (1).

Wednesday, June 17, 2009

Patients with irritable bowel syndrome (IBS) could find great relief from using dietary fiber, but how can clinicians make sure they get the right fiber?

A 2004 systemic review published in Ailment Pharmacol Ther improved means of advising patients with IBS on which fiber to take. The review included 17 randomized, controlled trials on both soluble (psyillium, ispaghula, calcium polycarbophil) and insoluble fiber sources (corn and wheat bran) (1). The researchers found that the soluble fiber sources were effective in providing relief to patients while insoluble fiber sources worsened symptoms in a few cases (1).

Based on these important findings, the Harvard University Medical School advised that soluble sources of fiber “are more effective” than that of insoluble for IBS in “alleviating global symptoms and relieving constipation, although fiber in general has marginal benefit” (2).

Tuesday, June 16, 2009

Cardiovascular disease and diabetes have several inter-related risk factors that may include obesity, high-cholesterol, high-triglycerides, hypertension, insulin resistance and inflammation (1). All these separate conditions can be treated in various ways. But why not lump them all together: metabolic syndrome?

Combining the cluster of risk factors into one condition remains controversial among scientists. On one side of the coin are those that metabolic syndrome provides a greater perspective for treating and managing reduction of all factors to avoid future problems (1;2). On the other side of the coin are those who find that evidence is not reliable enough and that more work is needed before risk factors can be chosen before defining metabolic syndrome as a clinical tool (3-6).

Clinicians, however, can rest assured that while research should continue into metabolic syndrome, the current definition of the condition can be helpful. According to a systemic review and meta-analysis published in 2007 by Mayo Clinic on 43 cohorts, there was a strong association of “increased risk of cardiovascular events” with those with metabolic syndrome (7). Thus, ultimately, the most recent data suggest that using metabolic syndrome as a clinical tool for treating and counseling patients shows great promise.

Monday, June 15, 2009

Who wouldn’t want a biscuit? Not a diabetic or anyone else fearing a high-glycemic response. Not more than one or two at least. But will a patented, highly viscous fiber blend change how we enjoy starchy-tasting snacks?

Croatian food scientists who have been studying the fiber blend reported that, when included as an ingredient in biscuits, it was successful in maintaining healthy blood sugar levels (1). The researchers tested the fiber biscuits on a small number of healthy and diabetic participants in a small randomized, controlled, single-blind, four-arm crossover trial published in 2008 (1).

The biscuits included 10 grams of the fiber blend and 50 grams of carbohydrates. They were compared in the study to 50-gram carbohydrate biscuits alone, white bread alone containing 66.8 grams of white flour, and of white bread with 12 grams of margarine (1).

Each participant was given each treatment after a 12-hour overnight fast (1). Finger-prick blood samples were then taken in four 15-minute intervals and one after 90 minutes (1). At least three days occurred between testing sessions (1).

The testing confirmed that there was no difference in palatability from including the fiber blend in the biscuits, but that gastric emptying was delayed effectively lowering the glycemic response of the biscuits significantly (1). In contrast, the 12 grams of margarine on the white bread had no effect on glycemic response (1).

The study reported that the results suggest the fiber blend could be used to “replace fiber depleted high fat snack foods” (1). The low-glycemic index snacks would then meet the needs of those with type 2 diabetes mellitus and those with cardiovascular disease (1).

The fiber blend was reported to be more effective in lowering glycemic response than other soluble fibers including psyllium hulls, glucomannan alone, beta-glucan, guar gum, pectin and ground flax seed (1).

From the looks of it I scored exactly 100 today. Hooray! I could've done better. I didn't realize honey would add so much. Had I only used blueberries and raspberries in my oatmeal, then it would have dropped to 80. Yes, I realize I could've also gone without the Frapuccino, but it looked so good this morning.

One way that I often use to help lower the glycemic response of high-GL foods is by having them with a complete meal that includes protein, fiber and "good" fats. When it comes to those high-GL beverages I try to include a flavorless soluble fiber supplement such as psyllium hulls or digestion-resistant maltodextrin.

Strong evidence exists that low-glycemic and low-glycemic-load diets reduce risk of diabetes mellitus, obesity, insulin resistance, cardiovascular disease and cancer (1-4). However, glycemic index and glycemic load are subject of controversy among nutritionists because they are inconsistent in their findings due to high variability, are poorly standardized and their results are difficult to reproduce (1;2).

Despite methodological problems, however, studies are showing glycemic index and glycemic load are effective as clinical tools (3-5). According to one systemic review of 11 randomized controlled trials of four weeks or longer, low-glycemic diets helped patients control glycemic response in diabetes (3). One randomized, controlled trial also showed that a low-glycemic load diet may be more effective than a conventional low-fat, reduced-calorie diet in reducing risk of cardiovascular disease (5).

Athletes have also found glycemic index and glycemic load to be useful in improving performance. Moderate- to high-glycemic carbohydrates consumed after exercise have been found to enhance glycogen storage, and it’s thought that consumption of low-glycemic, carbohydrate-rich foods hours before an endurance event may provide lasting energy, although more research is needed to support this theory (6-8).

Sunday, June 14, 2009

Most iron is stored in the liver, lymph and skeletal muscles by use of a protein, ferritin (1). Ferritin consists of an apoprotein called apoferritin that is made up of H and L subunits (amino acids) synthesized dependent on concentration of free intracellular iron (1). Each protein can hold up from 3000 to 4500 iron atoms (1). When overload exceeds storage capacity, however, a partially degraded form of ferritin in spheres occurs called hemosiderin (1p252, 2p825). An accumulation of iron deposits via hemosiderin results in hemosiderosis (3).

What causes hemosiderosis?

Hemosiderosis can be inherited by way of a genetic mutation such as Bantu siderosis or Ferroportin disease. Previously thought to occur due to drinking too much beer, Bantu siderosis affects up to 10 percent of rural Africans and is associated with cirrhosis, heart disease and diabetes (4). Ferroportin disease is the most common genetic hemosiderosis and caused by gene mutation that disrupts ferroportin production (4).

Pulmonary hemosiderosis occurs due to over-accumulation of iron in the lung tissue (4). It can be a result of cardiovascular disease or a systemic disorder that mostly affects children (5). Anemia, lung scarring and coughing up blood are all symptoms (4). Corticosteroid therapy has been successful as a treatment and iron therapy or transfusion is important (5;6).

Renal hemosiderosis, hepatic hemosiderosis or other organ-specific hemosiderosis may occur due to hemolysis, leaving iron from hemoglobin to collect in the organs (4). Its cause can genetic or by an agent of some kind, which can lead to hepatocyte distruction and liver disease (5-8).

Hemoglobin C disorder is a genetic missense mutation of hemoglobin resulting in a GAA or GAG codon for glutamate replaced with an AAA or AAG codon for lysine in the sixth position of a beta-globin (1p206). It is the most common hemoglobinopathy after sickle cell disorder (1p206).

What is pernicious anemia?

Pernicious anemia is not specifically an anemia, but a gastric disorder that can lead to megaloblastic anemia as well as neurological deterioration via demyelination of nervous tissue (1p1109, 2p483). The disorder was fatal until liver extracts were found in 1926 to be a cure (1p1109).

What is the cause of pernicious anemia?

The cause of pernicious anemia is lack of gastric intrinsic factor, which is required to absorb extrinsic factor cobalamin (vitamin B12), or a dietary deficiency of extrinsic factor cobalamin (1p1109, 2p483). Cobalamin is required for two enzymes in the body: methionine synthase, which drives homocysteine methylation to methionine, and methylmalmalonyl-CoA mutase, which drives conversion of methylmalonyl CoA to succinyl CoA (1p1109). Without cobalamin homocysteine and methylmalonic acid both accumulate causing the megaloblastic anemia (1p1109). The demyelination may be caused because methylmalonic acid inhibits and acts as a substitute for malonyl CoA in fatty acid biosynthesis (1p1110).

Dyshemoglobinemias are mainly caused by exposure to exogenous xenobiotics although it can be hereditary (1). The occurrence is result of altered hemoglobin (Hb) preventing its normal function of carrying oxygen (1). The anemia, hypoxia, cyanosis and associated problems can be life-threatening (2).

Causes

Acquired methemoglobinimeas occur when dysfunctional hemoglobin form methemoglobin, whereas mutated amino acids make up a wall against heme or form the site involved in binding oxygen (3).

Carboxyhemoglobinemia is a form that results of exposure to carbon monoxide or nitrous oxide poisoning (4-6). It can occur as a result of overexposure to automobile exhaust, smoke from a fire or tobacco or nitrous oxide (4-6).

Sulfhemoglobinemia is a serious form that can occur when overexposed to sulfonamides or sulfur compounds such as when taking certain drugs (2;7;8).

Detection

Pulse oximetry is a non-invasive way to detect dyshemoglobinemia through monitoring the oxygenation of the blood (9;10). Invasive approaches of carbon monoxide oximetry or blood gas analysis also exist (10;11). Symptoms include cognitive changes, headache, fatigue, dizziness and syncope (12). If methemoglobinemia is greater, then dysrhythmias, seizures or coma can occur (12).

Treatment

An obvious measure is to eliminate exposure to the causal agent. Oxygen therapy can be used to increase oxygen carried by normal hemoglobin and, in extreme cases, blood transfusions may be necessary (12).

Friday, June 12, 2009

Iron is abundant in the world and needed by every living organism. For this reason early in evolution multi-cellular organisms evolved antimicrobial peptides(1). Without them we just wouldn't be able to survive the onslaught of microbial growth (1).

In addition, free iron in plasma has redox capabilities that can also be toxic. The toxicity is due to the Haber-Weiss-Fenton sequence, which forms hydroxyl radicals due to superoxide after reduction of dioxygen (1). The hydroxyl radicals can then act detrimentally on proteins, nucleic acids, carbohydrates and also cause lipid peroxidation (1).

In animals, heme is the moiety that holds a central iron atom within a porphyrin ring structure (1). Most of the body’s iron is contained as heme acting in various functions, but mainly necessary as an oxygen carrier within hemoglobin of blood cells and myoglobin in muscles (1). Heme synthesis requires iron to be in a reduced ferrous state, which is why ferriductases are important for iron metabolism (1).

Of the total amount of iron received from the diet, only 10 percent is generally absorbed. Of clinical importance, dietary iron is best if derived from animal products, which contains heme iron (1). Nonheme iron, found in both animal and plant-based foods, is not absorbed as well, although absorption of nonheme iron is increased at times of iron deficiency (1).

Sunday, June 7, 2009

Just in case anyone's interested, I had the great opportunity to discuss nutrition science today with none other than Lucy discoverer Donald Johanson. What luck!

After explaining to Johanson of studying "evolutionary discordance" of diet post-agricultural revolution, he pointed me in the direction of a book related to hominin diets based on studies of hominin teeth.

This revelation led me to have a great interest in what further studies could be put together. I imagine randomized, controlled trials involving diets of humans on pre-human diets. Not only could the data help us better understand certain adaptions in our own digestive systems, but also what possible other "evolutionary discordances" that may have occured during a time when humans actually became human.

At the same event I spoke to another evolutionary biologist who suggested that fire had a key role in allowing our digestive system to adapt to a higher-energy diet.

The book recommended by Don Johanson was by Peter Ungar. A link to an article on the subject of diet and hominin teeth is found here.

Description: Researchers treated 204 patients with mild to moderate AD (ages 74 +- 9) with n-3 fatty acids or placebo for 6 months. All patients then received n-3 fatty acid treatment for the following 6 months. No cross-over trial was performed.

Patients were chosen for stability while on normal acetylcholine esterase inhibitor treatment and who had score of 15 points or more on a Mini-Mental State Examination (MMSE). During the study, the patients continued their regular treatment. Exclusions of the study included patients undergoing treatment with NSAIDs, other n-3 preparations or anticoagulants as also were those who had history of alcohol abuse or serious disease, or if did not have a caregiver.

The n-3 fatty acid treatment included 1.7g of docosahexaenoic acid (DHA) and 0.6 eicosapentaenoic acid (EPA) daily and the placebo group was treated with an isocaloric placebo of corn oil that included 0.6 g of linoleic acid daily.

Results: No statistical significant difference during 6 and 12 months for those with more advanced AD as revealed by MMSE and ADAS; however, a subgroup of mild dementia did show statistically significant treatment from MMSE scores over the duration of the study. The results found with the subgroup with mild dementia strongly suggest possibility of better cognitive performance and, perhaps, a role in “primary prevention of AD but not in treatment of manifest disease”.

Assessment: Despite lack of a cross-over trial included, this first-ever published randomized, double-bind, placebo-controlled study on treating AD with n-3 fatty acids presents valid data of excellent quality. The study, however, is limited in data on how differing amounts of n-3 fatty acids as well as differing ratios of EPA and DHA might have affected results. The researchers rightly suggest that more controlled intervention studies are needed to explore this area.

Description: Researchers searched Medline and Embase databases with relative keywords (e.g. “fish) to identify 9 total relevant cohorts (note: one study counted as two) published in English language journals from 1966 to 2003.

The cohort studies chosen each provided “relative risk” and “corresponding 95%” confidence interval factors for relationship of stroke with fish consumption. Duration average of each was 12.8 years with a range of 4 to 30 years. Each study had been properly adjusted for multiple covariates. Regional variance existed: of the 9 studies, 6 were from the U.S., 1 from Europe, 1 from China, and 1 from Japan creating a regional variance. Five of the studies attained data through personal interviews presenting variance with stratified analyses.

Disadvantages: The researchers note limitations in that most studies chosen “did not separate ischemic from hemorrhagic stroke”, which are different in etiology. It was noted that Japan and China studies presented a population of which may have higher risk of hemorrhagic stroke versus most studies from the U.S., where ischemic stroke is higher risk. Confounding variables from each cohort also must be taken into consideration.

Results: Review suggests “an inverse association between fish consumption and risk of stroke, particularly ischemic stroke, although there was not a strong dose-response relationship.”

Assessment: Large populations and different ethnic groups among the 9 cohorts introduce multiple variables that challenge this meta-analysis considerably. These would include, as noted in the study, even how and what kind of fish was cooked. The review also is limited in determining what amounts of fish should be eaten for most benefit or whether or not there was a relationship of stroke risk with amount of n-3 fatty acids.

Description: Beydoun et al (1) analyzed plasma fatty acids in cholesteryl esters and phospholipids in 2,251 white women and men ages 50-65 from 1987 to 1989 in a community in Minneapolis, MN. In subsequent years 1990 to 1992 and 1996 to 1998, researchers administered cognitive tests on the subjects.

Measurements: Blood analysis was performed through collection of 12-hour fasting blood followed by identity of peaks through gas chromatography. Reliability coefficient for the testing ranged from 0.50 to 0.93 for cholesteryl esters and from 0.50 to 0.89 for phospholipids.

Cognitive assessments included tests for delayed word recall, psychomotor speed and verbal fluency. The researchers properly noted that almost all subjects had education of high school or above, which was important to assure group comparability. Ages 65 and older were excluded to as not skew measurements as were those showing signs of early mental decline.

Problems: Disadvantages of this study were chiefly the amount of confounding variables, which required control through backward elimination. Despite the control and reducing subjects from initial 4,000 to the 2,251, the large amount of subjects introduced many covariates. As appropriate Beydoun et al reported a type 1 error level of 0.10 that was validated through statistical analysis.

Results: Study’s findings suggested n-3 fatty acids “may have substantial benefits in reducing risk of cognitive decline in the area of verbal fluency,” but did not suggest any benefit for psychomotor speed or delayed word recall. Further, findings revealed warranted enrichment of n-3 fatty acids in the diet of those with increased oxidative stress from hypertensive and dyslipidemia.

Assessment: Despite noteworthy effort on behalf of Beydoun et al to control variables by reducing the study to a homogenous population and by eliminating many covariates, the other multivariates acting as potential confounders leads me to agree with the researchers themselves that randomized, controlled, cross-over trials are necessary to determine more meaningful data.

Intrinsic factor, a glycoprotein secreted from paretal cells in the stomach, is responsible for forming a complex with cobalamin (B12) to then bind to an ileal receptor for absorption (1p1184). Lack of ability to secrete intrinsic factor results in pernicious anemia, a megaloblastic anemia from cobalamin deficiency(1;2). Pernicious anemia therapy often requires parenteral cobalamin or oral cobalamin in high enough doses (1).

Friday, June 5, 2009

Last night I met up with perhaps the most famous biologist on the planet, PZ Myers. How? He was just hanging out at a bar in town. Couldn't believe my luck! I brought up all my evolutionary nutrition ideas to him.

In case anyone's interested (does anyone read this blog?), PZ was fond of this recent article of Wrangham who wrote Catching Fire: How Cooking Made Us Human.

The book, by the way, pretty much shuts down the raw-foodist movement suggesting that cooking was absolutely essential for our species to get along in the world.

Also, I brought up archaeologist Curtis Marean's suggestion that "humans adapted to a life on the beach" eating shellfish and gaining omega-3 oils to form bigger brains.

PZ raised his eyebrows and said something like, "Humans are just too opportunistic to have been that limited in diet."

He went on to discuss amylase gene copy number variations of which I found fascinating. Nature article about it here.